This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to conduct a dose escalation safety and preliminary efficacy study of D-serine in subjects meeting criteria for schizophrenia with refractory negative symptoms. The goal of this study is to determine the tolerability and likely clinical responsivity to D-serine doses equal to and higher than those used in prior studies, and to examine the relationship between dose, plasma level, and clinical response measures.